The present invention relates to a method for encapsulating particles, and more particularly, to a method for encapsulating particles with a coating that substantially conforms to the size and shape of an individual particle utilizing selective withdrawal technology. The invention also includes specific uses for the particles encapsulated according to the inventive method.
Selective withdrawal technology involves the xe2x80x9cselectivexe2x80x9d withdrawal of the upper fluid, or both fluids, from a container holding two fluids of different densities. In most cases, this technology has been applied to combinations of fluids where the upper fluid is a gas, such as air, and the lower fluid is a liquid. Examples of such use of this technology are found in the oil industry.
When two fluids of different densities are added to a container, the less dense fluid floats on top of the fluid having a greater density, and an interface exists between the fluids. If it is desired to controllably withdraw the upper fluid only, or a combination of both fluids, a tube connected to a suction pump may be inserted into the upper fluid to suck up fluid from the vicinity of the orifice of the tube. At a low suction level, a slow flow of the less dense upper fluid layer enters the nozzle of the tube, and the more dense fluid remains in the container. The low level of suction generally causes a portion of the interface between the fluids to deform upwardly from its horizontal orientation to form a small hump in the area below the nozzle. Under these low suction conditions, the hump remains stable, and all of the withdrawn fluid comes from the upper layer.
If, however, the suction level is sufficiently increased, the hump becomes unstable and forms a spout at the interface of the two fluids. The spout comprises the heavier, lower layer, which is entrained in the lighter, upper layer. When a spout is formed, portions of the heavier fluid also enter the tube. The diameter of the spout decreases substantially from its base toward the tube orifice. Further increasing the suction level widens the spout. Once inside the tube, the spout breaks up into small droplets.
When applying this technology to combinations of fluids in which the upper fluid is air, the system is generally unstable. The spout is not stationary, and it often meanders and breaks apart in a disordered pattern. This lack of stability of the spout has hindered more widespread use of the selective withdrawal technology, since the instability makes it difficult to design processes that have an acceptable level of predictability and reproducibility. If more controllable use of this technology could be developed, the selective withdrawal technology could be put to more and better productive uses.
The present inventors have addressed the problems of the prior art by developing a selective withdrawal system in which the spout formed by the withdrawal of the entrained fluid is substantially stationary. As a result, the spout does not meander in a disorderly manner as in the example discussed above when air was used as the upper (withdrawn) fluid. It has been determined that such fluctuations of the spout can be reduced dramatically when air is replaced as the upper fluid by a fluid, such as a viscous liquid, more capable of supporting a stationary spout. When such a fluid is utilized as the upper fluid in a selective withdrawal system, a clean, reproducible and substantially stationary spout may be formed.
Due to the reproducible nature of the results in such combinations, the technology may be applied to areas where greater predictability of the action is required, such as the encapsulation of particles. When utilizing the method of the present invention, coatings may be applied to particles of varying sizes and shapes that substantially conform to the respective size and shape of the particles. A conformal coating of this type may be used for various applications in which uniform coatings of multi-sized particles are desired, such as the encapsulation of cells for transplantation. One example of such potential use is the microencapsulation of islet cells with a polymeric coating for transplantation into diabetic patients. The particles may be encapsulated with a coating that permits the transfer through the coating of useful compounds, such as glucose, insulin and metabolites, while preventing the transfer of compounds that may cause harmful interaction with the immune system. Similar uses may be possible for treatment of other conditions, which treatments have heretofore been hindered by undesirable immunogenic responses.
Another use to which this technology may be applied is the coating of particles for use in systems, such as drug delivery systems, in which timed release of a drug or other coated substrate is desirable. In such applications, particles can be coated to a predetermined thickness with a particular compound, or alternatively, a predetermined number of coatings of predetermined thickness and composition can be applied to the substrate.
In addition to the foregoing uses, other possible uses are described hereinafter. It should be understood that the specific uses described are merely intended to be illustrative of some of the uses to which the technology of the present invention may be applied. Those skilled in the art will appreciate that the present invention will have application to additional uses, all of which are considered to be within the scope of the present invention.